Improving the potency of DNA vaccine encoding HIV-1 Nef antigen using two endogenous adjuvants in mouse model.

BACKGROUND: DNA immunization can induce long-term immune responses, which are required to design an effective HIV vaccine. It was shown that antigen-expressing plasmids can increase the protective immunity against infectious diseases such as: influenza and malaria. However, DNA-based immunizations have poor immunogenicity, thus the use of potent immunoadjuvants can enhance their potency.

METHODS: In the current study, preparation of the recombinant HIV-1 Nef, Gp96 and HMGB1 DNA constructs was performed in bacterial system. Then, the immunogenicity of DNA construct harboring HIV-1 Nef gene (pcDNA-Nef) was studied using two endogenous adjuvants (pcDNA-HMGB1 and pcDNA-Gp96) in BALB/c mouse model.

RESULTS: Our data showed that co-injection of pcDNA-Nef with pcDNA-HMGB1 effectively raised both humoral and cell-mediated immune responses in mice as compared to pcDNA-Nef adjuvanted with pcDNA-gp96. Indeed, co-immunization of HIV-1 Nef DNA with HMGB1 DNA significantly induced high levels of IgG2a and IFN-γ directed toward Th1 responses and also cytotoxic T lymphocytes (CTLs) activity in comparison with other immunized groups.

CONCLUSION: These findings suggest that the full length of HMGB1 gene could be a more efficient adjuvant for improvement of therapeutic HIV DNA-based immunization compared to the full length of gp96 gene (Tab. 1, Fig. 3, Ref. 58).